592 



SCIENCE 



[N. S. Vol. XLV. No. 1171 



lias recently shown qnantitatively that during 

 the whole course of the development of the 

 follicles definite relations exist between the 

 ovum and the proliferation of the granulosa 

 cells. These relations can hardly be explained 

 in any other way than as dependent upon a 

 growth stimulus emanating from the ovum and 

 determining the proliferation of the granu- 

 losa cells and thus indirectly of the whole 

 follicle. It is possible that in addition to this 

 endogenous growth stimulus certain exogenous 

 stimuli, emanating from other organs with in- 

 ternal secretions (hypophysis?) may be opera- 

 tive. This effect of the ovum on the granulosa 

 cells leads to the formation of the cumulus 

 oophorus, and this structure makes possible 

 the escape of the ovum into the Fallopian 

 tube. Thus the ovum is ultimately the seat of 

 the mechanism which makes possible its fertil- 

 ization and fixation in the uterine wall. 



3. In previous investigations^ we have shown 

 that it is possible to cause a premature atresia 

 of follicles by the burning out of the corpora 

 lutea. While the effect of moderate heat does 

 not directly destroy the follicles, it diminishes 

 their expansive power ; they groW up to a cer- 

 tain point and then become prematurely 

 atretic ; the heat causes a mild degree of what 

 might be called a "tissue shock." Under 

 those conditions the development not only of 

 mature, but even of moderately sized follicles, 

 does not take place and as long as this condi- 

 tion lasts the animal is sterile. 



4. In continuation of these experiments we 

 found that it is possible to produce the same 

 condition not only by means of a local inter- 

 ference with the ovary, but also by affecting 

 the general state of nutrition through under- 

 feeding the animal. In all cases in which the 

 animals (guinea pigs were used in our experi- 

 ments) had lost 25 per cent, of their initial 

 weight maturation of the follicles ceased, and 

 in the majority of the cases the follicles be- 

 came atretic before they had reached even 

 medium size. The changes in the ovary were 

 on the whole more pronounced in younger ani- 

 mals weighing between 300 and 400 grams, 



1 Loeb, Leo, ZeniraVblatt f. PhUsiologie, 1911, 

 XXV., No. 9. Virchoios ArcUv, 1911, CCVI., 218. 



but in some cases very marked changes were 

 also produced in older animals. A certain 

 minimum time has to elapse before the changes 

 in the ovary become apparent. 



The lack of sufficient food affects in the 

 first place the granulosa cells; they prema- 

 turely dissolve. Those granulosa cells, how- 

 ever, which at first escape the solution, con- 

 tinue, as Dr. Walsh found, to divide at ap- 

 proximately the normal rate — another proof 

 of the distinctness of proliferative stimuli 

 and foodstuffs. 



The connective tissue becomes affected by 

 the underfeeding somewhat later than the 

 granulosa. This apparent difference in the re- 

 sistance of different tissues to the effects of 

 underfeeding is of interest and will be tested 

 in further experiments. Thus underfeeding, 

 if very marked, will lead to at least temporary 

 sterility in the guinea pig as an expression of 

 what we designated as a " hjTpotypical " condi- 

 tion of the ovaries. 



5. In one case of pronounced loss of weight 

 following thyroidectomy, we found a still 

 further reaching change. Not only were the 

 ovaries hypotypical, but the stroma separating 

 the various follicles had become affected. It 

 was underdeveloped or lacking in places, so 

 that the thecse internee of neighboring follicles 

 in places directly adjoined each other. As a 

 result of this condition and of an imperfect 

 separation of primordial ova, due to the same 

 relative inactivity of the connective tissue, 

 many follicles containing two or more ova 

 developed in both ovaries. It could be clearly 

 seen that small follicles were pushed into the 

 cavity of neighboring follicles as a result of 

 the intraovarian pressure, which, while dimin- 

 ished in hypotypical as compared with normal 

 follicles, was still positive and as a result of 

 the lack of development of ovarian stroma. 

 Follicles containing more than one ovum are 

 occasionally found in the ovaries of various 

 species and it would be of interest to determine 

 whether in addition to the factors operative in 

 our case, other factors may be responsible for 

 this condition in other cases. 



Leo Loeb 



Depaktment of Compaeative Pathology, 

 Washington University 



